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Biomedical subjects

A Gringeri

Publications and source records attributed to A Gringeri.

At least 91 records · Page 5Linked to original sources
PubMed1991

No activation of the common pathway of the coagulation cascade after a highly purified factor IX concentrate.

Purer factor IX concentrates, containing very little or no factor II or X, have been developed in an attempt to avoid the thromboembolic complications that occur with prothrombin complex concentrates (PCC), which also contain factors II and X and variable amounts of factor VII. To evaluate ex vivo the thrombogenic potential of one of these purer concentrates, we studied whether large single doses produced signs of activation of the coagulation cascade in patients with haemophilia B, and compared the results with those obtained after infusion of a PCC. Seven patients were infused with 50 IU/kg of factor IX concentrate and seven additional patients were subsequently infused with 100 IU/kg of the same concentrate. After the infusions, factor IX levels rose in proportion to the administered dose while the concentrations of factor II and factor X did not rise at all. At both doses of concentrate, we did not observe significant post-infusion increments in the levels of the factor X activation peptide (a measure of the activity of the factor VIIa-tissue factor complex and/or the factor IXa-VIIIa-activated surface complex), prothrombin fragment 1 + 2 (a measure of factor Xa activity), and fibrinopeptide A (a measure of thrombin activity). We also infused 10 patients with a PCC (50 IU/kg). After the infusions, significant rises in the concentrations of the factor X activation peptide and prothrombin fragment were observed. Therefore, it appears that the infusion of a PCC to patients with haemophilia B can augment factor X activation and subsequently thrombin generation in vivo and that this process can be abrogated by the administration of more pure factor IX concentrate.

Adolescent↗
PubMed1991

Failure of recombinant activated factor VII during surgery in a hemophiliac with high-titer factor VIII antibody.

Recombinant activated factor VII (rFVIIa) was used before and after inguinal hernioplasty to prevent bleeding in a patient with hemophilia A complicated by a high-potency antifactor VIII inhibitor. rFVIIa (75 micrograms/kg) was given before and after surgery, first by bolus infusions at intervals of 2-3 h for 47 h and then by continuous intravenous infusion at a rate of 38 micrograms/h for an additional period of 12 h. Although no undue bleeding was observed during and for the first 26 h after surgery, the patient subsequently developed wound bleeding and hematomas that necessitated blood transfusion and infusion of porcine factor VIII. This case indicates that rFVIIa is not always successful in patients with antifactor VIII inhibitor and that more experience is needed to establish the optimal doses at surgery.

Autoantibodies↗
PubMed1991

Suboptimal response to hepatitis B vaccine in drug users.

Fifty-five drug users institutionalized in a community for drug detoxification were vaccinated against hepatitis B virus (HBV) with a recombinant yeast-derived vaccine (Engerix B, Smith Kline Biologicals, Belgium). At 0, 1, and 6 months, 20 micrograms of vaccine was given in the deltoid to these patients, of whom 17 had no serum HBV markers, 15 had only the antibody to core antigen (anti-HBc), and 23 had anti-HBc and antibody to the surface antigen (anti-HBs) values lower than the allegedly "protective" value of 10 mIU/mL. Forty-one healthy controls were vaccinated in parallel. At month 7 (ie, 1 month after the third dose of vaccine), in 76% (13/17) of drug users with no HBV markers, 6% (1/15) of those with isolated anti-HBc, and 69% (16/23) of those with anti-HBc and nonprotective anti-HBs, protective anti-HBs titers (greater than or equal to 10 mIU/mL) developed, compared with 97% (40/41) of controls. At month 24, these rates fell to 43% for drug users with no HBV marker, 0% for those with anti-HBc, 31% for those with anti-HBc and anti-HBs, and 86% for controls. The drug users who did not respond to vaccination were more likely to be those with evidence of prior HBV infection and anergy to skin tests. This indicates that unresponsiveness to hepatitis B vaccine in drug users may be due to altered immunity.

Adult↗
PubMed1990

Thrombin generation is not increased in the blood of hemophilia B patients after the infusion of a purified factor IX concentrate.

Prothrombin complex concentrates (PCC), licensed for the treatment of hemophilia B, are known to carry a significant risk of thromboembolic complications. Although the reasons for thrombogenicity are not completely understood, several manufacturers have developed purified factor IX concentrates that contain negligible amounts of the other vitamin K-dependent factors. To evaluate whether or not the infusion of such a factor IX concentrate is followed by lesser activation of the hemostatic system than by the infusion of a PCC, we performed a series of coagulation assays on 11 hemophilia B patients before and after the administration of these two types of concentrate using a randomized cross-over design. The levels of prothrombin fragment F1 + 2, a sensitive measure of the in vivo cleavage of prothrombin by factor Xa, was significantly increased in plasma after PCC, but not after factor IX concentrate. Plasma fibrinopeptide A, a sensitive index of the enzymatic activity of thrombin on fibrinogen, also increased significantly after PCC but not after factor IX concentrate. The fragment B beta 15-42, a sensitive index of the enzymatic action of plasmin on fibrin II, did not change after either concentrate. There were also no differences in less sensitive coagulation measurements, such as plasma fibrinogen, antithrombin III, and fibrin monomers, nor in indices of platelet activation, such as beta-thromboglobulin and platelet factor 4. These findings show that the infusion of a purified factor IX concentrate can result in substantially less activation of the coagulation cascade than may be seen with PCC.

Adolescent↗
PubMed1990

Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients.

The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV-DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti-HBs and anti-HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV-DNA may coexist with markers thought to reflect immunity against HBV.

Adolescent↗
PubMed1990

Susceptibility to HIV infection and AIDS in Italian haemophiliacs is HLA associated.

We compared the frequencies of HLA antigens in two matched groups of 31 HIV-seronegative and 31 HIV-seropositive haemophiliacs, exposed during the years 1981-85 to comparable amounts and batches of presumably infectious clotting factor concentrates. The frequency of A2 was significantly higher in HIV-seropositive than in seronegative haemophiliacs, with a relative risk (RR) of seroconversion of 3.92, whereas both Bw52 and DR4 were negatively associated with it. We also studied the distribution of HLA antigens in a larger group of 76 HIV-seropositive haemophiliacs, who were at different clinical stages of HIV infection (CDC classes II-IV) but were comparable for age and time elapsed since seroconversion. DR3 and DQw2 antigens were, particularly when concomitantly present, associated with a high risk of developing symptomatic HIV infection (RR = 11.79 and 25.33). Our data suggest that the HLA region controls susceptibility to infection with HIV and its progression to symptomatic disease in Italian haemophiliacs.

Adolescent↗
PubMed1990

Low incidence of bleeding from HIV-related thrombocytopenia in drug addicts and hemophiliacs: implications for therapeutic strategies.

The records of 608 intravenous drug addicts and 124 hemophiliacs diagnosed in 1985 to be seropositive for HIV were reviewed to identify patients with thrombocytopenia. The records of 54 drug addicts (8.9%) and 14 hemophiliacs (11.2%) who had chronic thrombocytopenia were then followed through June 1989 to estimate the incidence of bleeding episodes. The records of 55 HIV-seronegative patients with idiopathic thrombocytopenic purpura (ITP), comparable for age, platelet count at diagnosis and duration of follow-up, were used for comparison. Patients with ITP were significantly different from those with HIV-associated thrombocytopenia in having a higher proportion of females (M/F ratio 13/42 v 53/15, p less than 0.001) and more intensive treatment (treated: 62% v 21%, p less than 0.001; splenectomized 37% v 1.5%, p less than 0.001). The incidence of major bleeding was not significantly different in drug addicts, hemophiliacs and ITP patients (0.98, 1.82 and 1.17/100 patients/year). Among drug addicts, bleeding was significantly more frequent in women than in men (3.4 v 0/100 patients/year, p less than 0.05). Our results indicate that the incidence of major bleeding in patients with HIV-associated thrombocytopenia is low and similar to that observed in more intensively treated ITP patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Immunogenicity of a yeast-recombinant hepatitis B vaccine in high-risk children.

Horizontal transmission of hepatitis B virus (HBV) from illicit drug users to their contacts, including young children, can be prevented by active immunization against HBV. Yeast-recombinant hepatitis B vaccines are now available for this purpose, but their potential efficacy in such high-risk contacts has not yet been evaluated. Therefore we gave 20 mcg of a recombinant yeast-derived hepatitis B vaccine to 38 children who were at high risk for HBV infection because they had been institutionalized in a community for drug users in which 8.7% of the occupants are carriers. After third dose of vaccine (at 0, 1, and 6 months), all children had anti-HBs responses with titers of 10 mIU/ml or more, with 81% showing responses greater than 1,000 mIU/ml. At 12 months, the percentage of anti-HBs-positive children was 100%, and the percentage of children with anti-HBs higher than 1,000 mIU/ml was 56%. None of the children developed HBV infection during follow-up. Hence the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers comparable with those attained in other categories of high-risk children with plasma-derived vaccines.

Adolescent↗
PubMed1989

Long-term immunogenicity of a plasma-derived hepatitis B vaccine in HIV seropositive and HIV seronegative hemophiliacs.

Short-term studies indicate that hepatitis B vaccines are safe and satisfactorily immunogenic in hemophiliacs. The duration of immunity in these immunocompromised patients, however, is not known. To determine this, we studied 78 hemophiliacs prospectively 2, 3, and 4 years after the initial vaccination with a plasma-derived vaccine given as three monthly injections followed by a fourth booster injection at month 14. The duration of immunity clearly depended on whether the patients were infected with the human immunodeficiency virus (HIV). In HIV seronegative hemophiliacs (n = 67), there was a progressive decline in titers of antibody to the hepatitis B surface antigen (anti-HBs), but antibody was still detectable 4 years later in all of them. From the curves of decline of antibody titers, it appears that there is no need to revaccinate patients for at least 5 to 6 years. The HIV seropositive hemophiliacs (n = 11) not only started from much lower anti-HBs titers, but 5 of 11 lost anti-HBs. None of the 45 patients treated with concentrates during the postvaccination period developed serologic signs of hepatitis B, even though 6 of them had come into contact with live or inactivated hepatitis B virus as shown by the occurrence of spontaneous anamnestic antibody responses. This vaccine and schedule of vaccination afford a prolonged duration of immunity in HIV seronegative hemophiliacs, but HIV seropositive hemophiliacs have a risk of losing immunity early.

Adolescent↗
PubMed1988

Diethyldithiocarbamate inhibition of murine bone marrow toxicity caused by cis-diamminedichloroplatinum(II) or diammine-(1,1-cyclobutanedicarboxylato)platinum(II).

We report here the effects of diethyldithiocarbamate (DDTC) rescue on myelotoxicity caused by carboplatin (CBDCA) and cisplatin (DDP) in C57BL/6 x DBA/2 F1 mice. All drugs were administered by injection into the tail vein. Myelotoxicity was assessed by WBC, bone marrow cellularity, and assays for pluripotent bone marrow stem cells (spleen colony forming unit) and granulocyte/macrophage progenitor cells (granulocyte/macrophage colony forming unit in culture). The most significant protection occurred in stem cells, where a single dose of DDTC (300 mg/kg) produced a platinum-drug dose modification factor of 3.3; i.e., the addition of DDTC reduced stem cell toxicity to the level produced by approximately one-third the dose of platinum drug alone. On a molar basis, DDP was 2.4 times as toxic to stem cells as CBDCA. The response of the stem cells to CBDCA and DDP was linear both with and without rescue, and the dose modification factor remained constant for doses of CBDCA up to 120 mg/kg and doses of DDP up to 15 mg/kg. Moreover, stem cell rescue appeared to be independent of DDTC dose (100-750 mg/kg) and time of administration (1.5 h before to 5 h after platinum drug). DDTC protection was less impressive for more mature hematological cells (granulocyte/macrophage colony forming units in culture). In studies of bone marrow cellularity, addition of DDTC (300 mg/kg) to DDP treatment (10 mg/kg) produced a 50% increase in the granulocyte-predominant cell population but had no effect on the lymphocyte population. Peripheral WBC showed no significant difference between rescued and unrescued groups and did not reflect the toxicity observed directly in the bone marrow.

Animals↗
PubMed1988

Immunogenicity of a recombinant hepatitis B vaccine in hemophiliacs.

Yeast-recombinant vaccines against hepatitis B virus (HBV) are now available, but there is no information about whether or not they are immunogenic in patients with hemophilia and other congenital bleeding disorders. Twenty micrograms of a recombinant vaccine expressing the adw serotype of the hepatitis B surface antigen (HBsAg) were given to 41 patients negative for HBV markers and again after 1 and 6 months. Ten percent of the vaccinees had anti-hepatitis B surface antibody (anti-HBs) responses, with titers of 10 mIU/ml or more, 1 month after the first dose of vaccine. The percentage of anti-HBs-positive patients increased to 54% after the second dose and to 98% after the third dose, with only one non-responder. Hence, the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers similar to those achieved with plasma-derived vaccines.

Adolescent↗
PubMed1986

Prevalence of HTLV-III/LAV antibodies in Italian asymptomatic hemophiliacs given commercial concentrates of factors VIII and IX.

The prevalence of HTLV-III/LAV antibodies was evaluated in 222 Italian asymptomatic hemophiliacs treated exclusively with commercial factor concentrates made with American plasma. An increase of HTLV-III/LAV seropositivity from 1983 to 1985 was evident. This was independent of the type of hemophilia (A or B) but directly correlated to the amount of concentrate administered in the previous year. Immunological data (T4 and T8 lymphocyte subsets) were evaluated in relation to seropositivity to HTLV-III/LAV. The presence of antibodies was found to be significantly associated with a low T4/T8 ratio and to a reduced T4 subpopulation, whereas increased levels of T8 lymphocytes correlated weakly with seropositivity. Data from 47 hemophiliacs tested both in 1984 and 1985 showed that 100% of those negative in 1984 and highly transfused in the previous year seroconverted up to 1985, whereas 33% of those not highly transfused did so.

Antibodies, Viral↗